quinonas mas

8/6/2019 Quinonas Mas

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Aromatics III: Reactions on Periphery


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O H K 2 C r 2 O7

H 2 S O 4

O

O

O H

K 2 C r 2 O 7

H 2 S O 4

O

O1,4-benzoquinone

p-quinone

O H

1,4-benzoqu inone

p-quinone

1,4-benzenediol hydroquinone

O H K 2 C r 2 O7

H 2 S O 4

O

1,2-benzoquinoneo-quinone

O H O

catechol

ON a2 S 2 O 4

H 2 O

O H

O H O

1,4-benzoquinone p-quinone

1,4-benzenediol hydroquinone


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Ox idation of Phenol to Quinones Phenols are subject to o x idation by a variety of strong o x idationagents, in part due to the electron donation - OH group.

Ox idation of phenol by potassium dichromate gives 1,4 benzoquinone ( p-quinone). Quinones are cyclohe x adienediones by definition and 1,2-quinones are called ortho while 1,3-quinonesare called meta.

Quinones can also be obtained by o x idation of catechol and 1,4- benzenediol (important trivial name: hydroquinone).

The most important property of quinones is that they are readilyreduced to benzenediols. p-Quinone can be readily reduced bysodium dithionate in neutral or alkaline solution.


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B iologically Relevant Quinones

Coenzyme Q ( Ox idized form) Coenzyme Q (reduced form)

An e x ample of the relevance of the o x idation/reduction cycle of quinones is the coenzyme Q (or ubiquinone, from ubiquitous).

Coenzyme Q is a carrier for electrons in the respiratory chain. Itresides in the mitochondrial inner member, noncovalently anchored

by its isoprene tail (unsaturated chain of si x to ten units).

Coenzyme Q is a two electron o x idizing agent. In subsequent stepsof the respiratory chain the reduced coenzyme Q trransfers twoelectrons to another linking molecule, until they are eventuallydelivered to o x ygen, which is finally reduced to water.

O

O

O

O

C H 3

C H 3

C H 3

H n

+ 2H + + 2e -

O H

O H

O

O

C H 3

C H 3

C H 3

H n


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S chematic of the electron transport chain (housed in themitochondrial inner membrane) and the role of Coenzyme Q

(CoQ )


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O

O

C H 3

H 7

Another important qunione is vitamin K 2. This vitamin isessential to the biosynthesis of prothrombin, a clotting agent, thattakes place in the liver.

Vitamin K 2

The natural vitamins of the K family have for the most part beenreplaced by synthetic preparations in food supplements.Menandione, an analog with vitamin K activity has a hydrogenin the place of the isoprene tail. Menandione can be preparedfrom 2-methyl naphthalene via a chromic acid o x idation under mild conditions.

C H 3

O

O

C H 3C rO 32-methyl-1,4-naphthoquinone

Menandione


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Reactions at the B enzylic Position

The benzylic position, as shown earlier, is a carbon directlyattached to a phenyl ring. This carbon is especially active due toresonance stabilization of the benzylic radical or cation.

C H 2 the benz ylic position

C C C C

resonance stabilization of benzylic cation

S imilar structures can be drawn for the benzylic anion andradical. B enzylic contributing structures are closely analogous

to allylic structures in stabilizing cations, anions and radicals.


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Ox idationB enzene is unaffected by strong o x idizing agents such as H 2Cr O 4and KMn O 4. Toluene, however, reacts under vigorous conditionswith these agents to give benzoic acid.

C H 3

H 2 C r

4

C O O H

benzoic acid

H alogen and nitro substituents are unaffected by these o x idationconditions, therefore substituted benzoic acids can be formedunder these conditions.

C H 3

H 2 C r O 4

C O O H

N O 2

B r

C l

N O 2

B r

C l

4-bromo-5-chloro-2-nitrobenzoic acid 4-bromo-5-chloro-2-nitrotoluene


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E thyl and isopropyl side chains are also o x idized to carbo x yl groups,however tert -butylbenzene is not o x idized.

C

H 2 C rO4

H 3C C H 3

C H 3

1-tert-butylbenzene

The mechanism of these o x idations are difficult to confirm;however, evidence suggests the formation of unstableintermediates, either benzylic cations or radicals.

Lastly, Naphthalene can be o x idized to phthalic acid by o x ygen anda vanadium pento x ide catalyst (V 2O 5 ). This industrial processillustrates the ease of o x idation of condensed benzene ringscompared with benzene itself. C O O H

C O O H

V 2 O5

350 oC

naphthalene phthalic acid

These Reactions are all

fair game for the Final!

CH 2 H 2 C rO4

CH 3

ethylbenzene

C O2 H

benzoic acid


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H alogenation

Toluene reacts in the presence of chlorine with light or heat to givechloromethylbenzene and H Cl (akin to the allylic radicalhalogenation we studied earlier).

B romination of the benzylic postion can be accomplished with N- bromosuccinimide in the presence of pero x ides.

C H 3

C l 2

H 2 C

heat or light

C l

+ H C l

1-(chloromethyl)benzene

C H 3 H 2 C B r N Br

O

O

(P hC O 2 )2 + N H

O

O

1-(bromomethyl)benzene

NBS

This S et of Reactions is fair game for the Final!


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H alogenation of a longer alkyl side chain is highly regioselective, asillustrated by the halogenation of propylbenzene. When treated

with N BS only the monobromo product is formed.When ethylbenzene is treated under radical conditions with chlorinetwo products are formed in a 9:1 ratio.

C H 2 H 2 C

C H 3

C H H 2 C

C H 3

N

r

O

O

(

hC O 2 )2

r

1-(1-bro opropyl )benzene1-propylbenzene

C H 2 C l 2

C H

heat or l ight

C l H 3C H 3C C H 2 H 2 C

C l

+

1-e thy lbenzene 1- (1-ch loroe thy l )benzene9 0 %

1-(2-ch loroe thy l )benzene1 0 %


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Therefore chlorination of the benzylic position isnt asregioselective as bromination. The same pattern was observed

with radical halogenation of alkanes.From these (and related) e x periments, we can predict the productdistributions based on the relative order of radical stability for hydrocarbons and vice versus.

methyl < 1 o < 2 o < 3 o < allylic benzylic

increasing radical stability


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H ydrogenolysis of B enzyl E thers

B enzylic ethers are unique among ethers in that they can be cleavedunder the conditions of catalytic hydrogenation.

B enzyl ethyl ether can be cleaved to toluene and ethanol byhydrogenolysis. In the hydrogenolysis of a benzylic ether, thesingle bond between the benzylic carbon and the o x ygen is cleavedand replaced by a carbon hydrogen bond.

C H 2 O

C H 2 H 3C

1-(ethoxy ethyl )benzene

CH 3

+ H 3C H 2 C O H

ethanol

H 2

d/C

This Reaction is fair game for the Final!


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B enzyl ethers can be prepared from an alcohol or a phenol bytreatment with benzyl chloride in the presence of a base

(triethylamine or pyridine).B enzyl ethers are particularly valuable as protecting groups for the - OH group of alcohols or phenols.

The synthesis of 2(-3-hydro x ypropyl)phenol shows how an acidic phenol is protected so that an alkene can be transformed into analcohol.

O H

PhC H 2 C l

pyridine O

1 . BH 3 T H F

2 .H

2 O

2 / N

aO H

O

O H

H 2

P d/ C O H

O H

2-(3-hydroxypropyl)phenol

This Reaction is useful for synthesis and fair game for the Final!


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S ome Nomenclature (For Fun!)

N O

N O

N O

O N

O N

N O

N

O

I N

OF e

F e

F e

F e

F e

F e

C H 3

C H 3

DO C

DO C

DO C DO C

DO C

DO C


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Now, Lets Review a B it by Doing a Couple of S ynthesis Problems

S tarting from phenol and any other stable, organic monofunc tional moleculecontaining four or fewer carbon atoms, provide a synthesis of each of thefollowing products. You may use any standard reagents you need as long as theyare not a source of more than four carbon atoms. (Monofunctional means onealkene, one hydro x yl, one bromo derivative, etc. but not two such groups or amix ture of groups.)

O O H O C HOOC HO

O

O

Plan: Dr. Sessler will post possible answers on the web ina day or two so you can practice. Well also go over these

during office hours on Monday if there is interest.


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S tarting from any stable, monofunctional organic molecule containing four or

fewer carbon atoms, provide a synthesis of each of the following products. Youmay use any standard reagents you need as long as they are not a source of morethan four carbon atoms.

O O O O

O H

OO H HO

H H

A Couple of More S ynthesis Problems to Play With

Plan: Dr. Sessler will post possible answers on the web so you can practice.


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I E njoyed the Class and H ope you did Too!

Good Luck on the Final!Good Luck on the Final!

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